A 10-mL round-bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (INTERMEDIATE AB) (48.92 mg, 0.089 mmol), thiazol-4-amine hydrochloride (Accel Pharmatech, East Brunswick, N.J., 15.78 mg, 0.116 mmol), and THF (889 μl) to give a suspension. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (293 μl, 0.293 mmol) was added dropwise over 30 s to give a bright orange mixture. The mixture was stirred for 5 min, then the flask was lowered into an ice-water bath. After 2 h, additional portions of thiazol-4-amine hydrochloride (15.78 mg, 0.116 mmol) and lithium bis(trimethylsilyl)amide (1M in THF) (293 μl, 0.293 mmol) were added in sequence. Following an additional 1 h of stirring, the mixture was quenched with glacial acetic acid (1 drop), diluted with MeOH, and concentrated in vacuo. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (14.11 mg, 0.030 mmol, 34.0% yield) as a tan solid: 1H NMR (400 MHz, DMSO-d6) 6=10.96 (s, 1 H), 8.88 (d, J=2.2 Hz, 1 H), 8.41 (d, J=1.7 Hz, 1 H), 8.09 (dd, J=1.9, 8.8 Hz, 1 H), 7.72 (d, J=8.7 Hz, 1 H), 7.30 (d, J=2.2 Hz, 1 H), 7.20 (dd, J=2.2, 8.6 Hz, 1 H), 6.99 (d, J=2.2 Hz, 1 H), 6.79 (d, J=8.6 Hz, 1 H), 4.38-4.28 (m, 2 H), 3.90-3.81 (m, 2 H); m/z (ESI) 467.2 (M+H)+.
